Establishment of true niacin deficiency in quinolinic acid phosphoribosyltransferase knockout mice

Abstract

Pyridine nucleotide coenzymes are involved in >500 enzyme reactions and are biosynthesized from the amino acidL-tryptophan (L-Trp) as well as the vitamin niacin. Hence, ''true'' niacin-deficient animals cannot be ''created'' using nutritional techniques. We wanted to establish a truly niacin-deficient model animal using a protocol that did not involvemanipulating dietary L-Trp. We generated mice that are missing the quinolinic acid (QA) phosphoribosyltransferase (QPRT)gene. QPRT activity was not detected in qprt-/- mice. The qprt+/+, qprt+/- ,or qprt-/- mice (8 wk old) were fed a completediet containing 30 mg nicotinic acid (NiA) and 2.3 g L-Trp/kg diet or an NiA-free diet containing 2.3 g L-Trp/kg diet for 23 d. When qprt-/- mice were fed a complete diet, food intake and body weight gain did not differ from those of the qprt+/+ andqprt+/- mice. On the contrary, in the qprt-/- mice fed the NiA-free diet, food intake and body weight were reduced to 60%(P <0.01) and 70% (P <0.05) of the corresponding values for the qprt-/- mice fed the complete diet at d 23, respectively. The nutritional levels of niacin, such as blood and liver NAD concentrations, were also lower in the qprt-/- mice than in the qprt+/+ and the qprt+/- mice. Urinary excretion of QA was greater in the qprt-/- mice than in the qprt+/+ and qprt+/- mice (P <0.01). These data suggest that we generated truly niacin-deficient mice. © 2012 American Society for Nutrition.